The long term objective is to provide a quantitative understanding of the myogenic and neurogenic processes which regulate gastrointestinal smooth muscle activity in experimental animals and in man. Smooth muscle from the internal anal sphincter, ileocolonic/ileocecal sphincter, muscularis mucosa of the esophagus, small and large intestines and the inner and outer circular muscle lamellae will be used. The areas of particular interest are: (1) the electrophysiological properties of the smooth muscle cell membrane in each of these areas; (2) the electrophysiological characteristics of neuroeffector responses; (3) the pattern of intramural innervation; (4) the identity of the neurotransmitters which cause excitation and inhibition; and (5) the electrophysiological and neurotransmission processes in normal and diseased human GI smooth muscle. The methods of approach will involve recording simultaneously mechanical and intracellular electrical activity, the recording of contractility of strips of muscle, radio-immunoassay of muscle to identify the type and content of peptides and radio-immunological and immunological techniques to identify the excitatory and inhibitiory transmitters. In vitro studies are planned. Dogs, cats, rabbits, guinea pigs and human GI smooth muscle will be used. These studies may be particularly relevant to understanding motor disturbances involving hypoganglionosis of the intrinsic plexuses in man. They man also be relevant to disturbances in anal continence in man.